Feasibility of Total Neoadjuvant Treatment With HYPErthermia in Patients With High-risk Extremity and Trunk Soft Tissue Sarcoma (TNT-HYPE)

Main Inclusion Criteria: * Histologically confirmed primary high-risk Soft tissue sarcoma (STS) of extremity or trunk. * High-risk according to the prognostic Sarculator tool: 10-year OS probability \< 60%5. * Resectable tumor: resectability is based on pre-operative imaging and has to be defined by the local treating sarcoma team. A patient is not considered resectable when the expectation is that only a R2 resection is feasible. * Measurable disease per RECIST v1.1. * Diagnostic biopsy is available for the central pathology review. * Candidate for chemotherapy regimen according to protocol. * Candidate for loco-regional HT. * Adequate bone marrow function, hepatic function, renal function, cardiac function and coagulation function. Main Exclusion Criteria: * Metastatic disease. * Previous Whoops resection. * Ex-ulcerating tumors or tumors infiltrating the skin. * Other invasive malignancy within 5 years, with the exception of adequately treated non melanoma skin cancer, localized cervical cancer, localized and Gleason ≤ 6 prostate cancer. * Any previous radiotherapy (RT) or systemic therapy for the present tumor. * Previous treatment with maximum cumulative doses (450 mg/m² doxorubicin or equivalent 900 mg/m² epirubicin) of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones. * Concomitant or recent (within 30 days of registration) treatment with any other experimental drug. * Concomitant use of other anti-cancer drugs or RT. * No metal implants in the region of tumor or cardiac implant electronic devices (CIEDs). * Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV), unstable angina pectoris, history of myocardial infarction within the last 12 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia), significant QT-prolongation, uncontrolled hypertension. * Active and uncontrolled infections, in particular urinary tract infections. * Inflammation of the urinary bladder (interstitial cystitis). * History of cerebrovascular accident or intracranial hemorrhage within 6 months prior to registration. * Vaccination with live vaccines within 30 days prior to registration. * Known hypersensitivity to trial drug(s) or to any component of the trial drug(s).